Tissue engineering is a field in which the principles of biology, engineering, and materials science are applied to the development of functional substitutes for damaged tissue. (See, Langer, et al., "Tissue Engineering", Science, 1993, 260, 920). In general, three different strategies have been adopted for the creation of new tissue: (i) isolated cells or cell substrates, in which only those cells that supply the needed function are replaced; (ii) tissue-inducing substances, such as signal molecules and growth factors, and (iii) cells placed on or within matrices. Researchers have been interested in applying these novel techniques to find replacements for tissues such as ectodermal, endodermal, and mesodermal-derived tissue. In particular, researchers are invested the replacement of tissues in the nervous system, cornea, skin, liver, pancreas, cartilage, bone, and muscle to name a few.
One specific area of interest for the use of tissue engineering techniques is in bone regeneration and repair. Over 1 million surgical procedures in the United States each year involve bone repair. Bone defects can result from diverse causes such as trauma, birth defects and disease pathoses. Current methods rely on an adequate supply of autogenous (from a donor site) and/or allogenic (from a human cadaver) bone. However, removal of autogenous bone for the grafting procedure requires surgery at a second site and also involves blood loss, pain and increased morbidity. Furthermore, for allografts, there exists the potential for disease transmission or host rejection. Thus, the search for alternatives to autografts and allografts in bone repair and regeneration remains an important topic in medical research.
A variety of biologically compatible materials have been tested for use in bone repair. The materials include naturally occurring compounds such as tricalcium phosphate or hydroxyapatite porous ceramics (Yoshikawa et al., Biomed. Mater. Eng., 1997, 7, 49; Ohgushi et al., J Biomed. Mat. Res., 1990, 24, 1563), and synthetic materials including absorbable lactide and glycolide polymers (Ishaug, et al., J Biomed. Mater. Res., 1997, 36, 17; Ashammakhi et al., Biomaterials, 1996, 18, 3), and ceramic bioglasses (Yamamuro, T., Bone-bonding behavior and clinical use of A-W glass-ceramic, in Bone Grafts, Derivatives and Substitutes, M. Urist, O'Connor, B. T., Burwell, R. G., Ed. 1994, Butterworth-Heinemann: Oxford U.K.). The existing technology, using biomaterials, though effective in many cases, is still beset with numerous difficulties and disadvantages. Thus, there still remains a need for improved methods in treating bone defects.
In 1953, Yasuda discovered an interesting property in bone (Yasuda, I., J Kyoto Med. Soc., 1952, 4, 395). He first reported that upon mechanical deformation of bone, electricity was produced upon mechanical deformation of bone, a phenomenon known as the "piezoelectric" effect. He showed that the mechanical loading of bone induced electromagnetic potentials or fields that could alter bone metabolism and produce an increase in bone mass and/or structure (Yasuda, I., J Kyoto Pref Univ. Med., 1953, 53, 325). Fukada, Becker, Bassett and others have suggested that the electrical activity observed in bone is a probable mediator of its repair and adaptive remodeling in response to mechanical loading (FIG. 1) (Fukada et al., J Phys. Soc. Japan, 1957, 12, 1158; Becker et al., "The Bioelectric Factors of Controlling Bone Structure", in Bone Biodynamics, R. Bourne, Ed., 1964, Little, Brown and Co.: New York; Bassett et al., Nature, 1964, 204, 652). Furthermore, these authors have observed that an exogenous electrical stimulus alone can stimulate bone regeneration (Lavine et al., Nature, 1969, 224, 1112; Humbury et al., Nature, 1971, 231, 190; Becker et al., Clin. Orthop. Rel. Res., 1977, 129, 75; Bassett et al., Clin. Orthop. Rel. Res., 1977, 124, 128; Brighton et al., Clin. Orthop. Relat. Res., 1977, 124, 106; Watson et al., Jap. J Appl. Phys., 1978, 17, 215; Bassett et al., Science, 1979, 184, 575). The early success of these experiments with direct current and electromagnetic induction finally led to widespread clinical treatments of non-union bone fractures. However, localization of the electrical stimulation, which is critical to effective treatment, still remains a challenge (Spadaro, J. A., Bioelectromagnetics, 1997, 18, 193). Therefore, a system whereby one can externally control and regulate the stimulus would be extremely attractive.
Clearly, there remains a need to develop systems and methods whereby biological activities of cells, such as, but not limited to cell growth, can be stimulated by direct application of electromagnetic stimulation. This would be particularly important in applications to tissue engineering.